6-64611796-A-G

Variant names:

• chr6-64611796-A-G
• rs604490
• NM_001142800.2:c.3684+5622T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142800.2(EYS):​c.3684+5622T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,088 control chromosomes in the GnomAD database, including 50,457 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (50457 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 0 publications found

Genes affected

EYS (HGNC:21555): (eyes shut homolog) The product of this gene contains multiple epidermal growth factor (EGF)-like and LamG domains. The protein is expressed in the photoreceptor layer of the retina, and the gene is mutated in autosomal recessive retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

EYS Gene-Disease associations (from GenCC):

• EYS-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• retinitis pigmentosa 25

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142800.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.3684+5622T>C		intron	N/A	NP_001136272.1
	EYS	NM_001292009.2		c.3684+5622T>C		intron	N/A	NP_001278938.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.3684+5622T>C		intron	N/A	ENSP00000424243.1
	EYS	ENST00000370621.7	TSL:1	c.3684+5622T>C		intron	N/A	ENSP00000359655.3
	EYS	ENST00000330816.5	TSL:3	n.305+5622T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122942 AN: 151970 Hom.: 50392 Cov.: 32

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.756

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.809 AC: 123066 AN: 152088 Hom.: 50457 Cov.: 32 AF XY: 0.809 AC XY: 60098 AN XY: 74324

African (AFR) AF: 0.951 AC: 39517 AN: 41532

American (AMR) AF: 0.789 AC: 12041 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2573 AN: 3466

East Asian (EAS) AF: 0.662 AC: 3424 AN: 5172

South Asian (SAS) AF: 0.837 AC: 4035 AN: 4822

European-Finnish (FIN) AF: 0.744 AC: 7862 AN: 10574

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.754 AC: 51244 AN: 67958

Other (OTH) AF: 0.758 AC: 1597 AN: 2108

Alfa AF: 0.761 Hom.: 19667

Bravo AF: 0.818

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.6
DANN	Benign	0.69
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs604490; hg19: chr6-65321689;